Macrophagic "crown-like structures" are associated with an increased risk of breast cancer in benign breast disease

In breast adipose tissue, macrophages that encircle damaged adipocytes form "crown-like structures of breast" (CLS-B). While CLS-B have been associated with breast cancer, their role in benign breast disease and early carcinogenesis is not understood. We evaluated breast biopsies from three age-matched groups (n = 86 each, mean age 55 y), including normal tissue donors of the Susan G. Komen for the Cure® Tissue Bank (KTB), and subjects in the Mayo Clinic Benign Breast Disease (BBD) Cohort who developed cancer (BBD cases) or did not develop cancer (BBD controls, median follow-up 14 y). Biopsies were classified into histologic categories, and CD68-immunostained tissue sections were evaluated for the frequency and density of CLS-B. Our data demonstrate that CLS-B are associated with benign breast disease: CLS-B-positive samples were significantly less frequent among KTB biopsies (3/86, 3.5%) than BBD controls (16/86=18.6%, p = 0.01) and BBD cases (21/86=24%, p = 0.002). CLS-B were strongly associated with body mass index (BMI); BMI < 25: 7% CLS-B-positive, BMI 25-29: 13%, and BMI ≥ 30: 29% (p = 0.0005). Among BBD biopsies, a high CLS-B count (>5 CLS-B/sample: 10.5% (BBD cases) vs 4.7% (BBD controls), p = 0.007) conferred a breast cancer odds ratio of 6.8 (95% CI: 1.4-32.4), p=0.02, after adjusting for adipose tissue area (cm2), histologic impression and body mass index. As high CLS-B densities are independently associated with an increased breast cancer risk, they may be a promising histologic marker of breast cancer risk in benign breast disease.

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